The authors wished to determine whether secretory cell metaplasia (SCM) induced in the bronchi of hamsters by human neutrophil elastase (HNE) was enzymatically mediated. We also wished to determine whether SCM could be induced by a proteolytic enzyme devoid of elastolytic activity. Accordingly, groups of weight-matched hamsters were given a single intratracheal instillation of 0.5 ml of saline solution containing one of the following: 300 micrograms of HNE purified from blood neutrophils, n = 14; 300 micrograms of HNE inactivated with Suc-Ala-Ala-Pro-Val chloromethyl ketone (CMK), n = 10; 500 micrograms of porcine pancreatic trypsin treated with CMK to eliminate residual active elastase, n = 10; 500 micrograms of trypsin inactivated by tosyl lysine chloromethyl ketone, n = 10; 2 micrograms CMK, n = 10; and saline alone, n = 10. Seven untreated animals served as additional controls. Twenty-one days post treatment, 5-6 micron paraffin-embedded sections, from the left lung hilar region, stained by Alcian blue and periodic acid-Schiff reaction were graded on a five-point scale for determination of the secretory cell index, which reflects SCM. Both elastase and trypsin produced severe SCM: mean +/- SEM secretory cell indices were 2.96 +/- 0.11 and 2.72 +/- 0.19, respectively, compared with values of 0.90 +/- 0.35 for the untreated group and 0.93 +/- 0.46 for the saline group (p less than .05). The secretory cell indices of the groups treated with inactivated elastase or trypsin were comparable to those of the saline-treated and untreated groups.(ABSTRACT TRUNCATED AT 250 WORDS)